The present invention is directed to a method of diagnosing Alzheimer's Disease in human beings. Alzheimer's disease is the fourth leading cause of death in the United States, the precise cause of which is not yet known. At present, it is a difficult and time-consuming task to definitively determine whether a patient is suffering from Alzheimer's disease or another ailment having similar manifestations and/or symptoms. Presently-used techniques for determining Alzeimer's Disease include neuropsychological testing which compares the mental status of the patient relative to a norm, as well as the patient's cognitive dysfunction. Such testing also tests for mood depressions, agitation, irritability, and the like, all of which are symptoms of Alzheimer's disease when combined with other diagnostic indications. These other diagnostic tools and methods are: The use of a brain atlas beam test or EEG (electroencephalogram) which demonstrate increases in delta and theta waves. Further, CAT scans of the brain or nuclear magnetic resonance (NMR) are used in the diagnosis by showing reduced uptakes of the brain's cells in the temporal areas or at the hippocampal region, which is a sign of cortical atrophy, associated with Alzheimer's disease, since the cortex and hippocampus of the brain are those usually affected by Alzheimer's disease, such effect being caused, it is believed, by the deficiency of the enzyme choline acetyltransferase (CAT). Choline acetyltransferase is the chemical messenger from the nucleus basalis to the cortex. Still another method used in the diagnosis of Alzheimer's disease, based upon the fact that it has been discovered that in Alzheimer's patients the brain is found to have consumed from 30%-50% less glucose in each of the four cortical regions and one subcortical region is the PET scan. The reduction of consumption of glucose in these portions of the brain is, it is generally believed, to result from the deficiency of the enzyme phosphofructokinase, which is necessary for the conversion of glucose to high-energy intermediates. The determination of glucose reduction in these portions of the brain is typically carried out by the PET scan, which detects the presence of the glucose analogue (F-18)-2-fluoro-2-deoxy-D-glucose (FDG).
It has hitherto been the conventional practice of determining a diagnosis of Alzheimer's disease by the positive indication by any of the above-mentioned tests. However, the results of these tests are often not definitive, since any one or more of them may show that the symptoms are not those of Alzheimer's disease even though the patient may be suffering therefrom. On the other hand, each of the above-mentioned tests may show that the diagnosis is that of Alzheimer's disease, when, in fact, it is not. The frequency of these false positives may be high. For example, a false positive may occur if the patient is suffering from neurosyphylis, follic acid deficiency, Vitamin B12 deficiency, hypothyroidism, encephalitis, electrolyte imbalance, drug toxicity, other metabolic disorders, virus infection of CNS, as well as others.
It is, of course, most important that a correct diagnosis be determined in order to decide upon the best treatment. The present invention is directed to a novel diagnosis for Alzheimer's disease that may be used in conjunction with other standard testing methods, or may be used alone for such determination, since it has been found to be very accurate, especially in conjunction with the fact that the other known diseases by which similar indications may result, as to those of the method of the present invention, are not at all likely to affect the patient for whom Alzheimer's disease may be a likely diagnosis.
It has been known that the drug levadopa (L-dopa), a common drug for treating Parkinson's disease, causes increased secretion of the growth hormone somatotropin (HGH-human growth hormone). This finding of L-dopa's provocative stimulation of the pituitary gland to secrete HGH was used as the basis for viewing the functioning of the peripheral nervous system (PNS) as an aminergic neuronetwork. Furthermore, since the hormone somatomedin-C (often referred to as IGF-I, for insulin-like growth factor, since it resembles insulin in many ways) is directly dependent upon the secretion of HGH by the pituitary gland, there has been established a direct linkage between increased secretion of HGH and increased production of the hormone somatomedin-C, which is produced chiefly in the liver and kidneys. The use of L-dopa to markedly increase the secretions of somatotropin and, consequently, the production of somatomedin-C in the human body has led to what is generally termed the "L-dopa provocative test." This test is used to determine the normal functioning of the anterior region of the pituitary gland responsible for the HGH production. Generally, the L-dopa provocative test is used by detecting the increases of HGH and IGF-I in a blood serum by the use of radioimmunoassay (RIA), which determines the presence or absence or the amounts of a certain hormone in a serum by the use of a radioactive agent, used in vitro. Radioimmunoassay techniques were first discovered by the observation that unlabelled insulin displaces radioactive iodine-labelled insulin from insulin antibodies, in vitro. With the antibody concentration and radiodinated antigen held constant, the binding of the label is quantitatively related to the amount of unlabelled antigen that is added. Thus, any amount of an unlabelled antigen may be determined by the known standards therefor. The amount of unlabelled antigen in a serum-sample can be guaged by measuring the fraction of bound, labelled antigen in its presence from a standard. RIA involves separation of the labelled antigen that is of interest into bound-unbound fractions after the interaction with an antibody in the presence of the unknown quantity of unlabelled antigen to be measured. RIA has been used in the past for the measuring of the amount of HGH in a serum taken from a subgroup of children, for treating diseases in children related to growth. The radioactive element used in this determination is usually I-125.
Somatotropin is a growth hormone (polypeptide link amino acid in character) secreted by the anterior region of the pituitary gland, which is most known for its capability of causing growth of the human skeleton. This is also known as the human growth hormone (HGH), and is the precursor of the hormone somatomedin-C (IGF-I), produced by the liver and kidneys. According to the present invention, it has been discovered that patients suffering from Alzheimer's disease have a deficiency of somatotropin production which leads to a deficiency of somatomedin-C levels, and that exogenous stimulation by a drug to cause increased secretions of HGH in normal human subjects does not function normally in Alzheimer's patients. Though it has been known to have increased levels of IGF-I in the blood with reduced levels of HGH, these instances are rare and can be taken into consideration when determining the diagnosis according to the present invention.
In applicant's copending application Ser. No. 666,254, filed on Oct. 29, 1984, it is disclosed that a method of treating Alzheimer's disease is by the administration of somatotropin, plus other anabolic hormones (Sex anabolic hormone, somatomamotropin, placental lactogen, trophoblastic hormonal factor).